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Biomedical subjects

C Holt

Publications and source records attributed to C Holt.

At least 73 records · Page 4Linked to original sources

Hypokalemia-induced psychosis in a chronic schizophrenic patient.

An association is documented between hypokalemia and an acute psychotic decompensation in a patient with chronic schizophrenia. The patient's symptom picture and other aspects of the clinical presentation alone were not sufficient to differentiate between hypokalemic psychosis and an exacerbation of schizophrenia. A restricted focus on a history of psychosis, ignoring the possibility of organic factors, can be misleading and dangerous to the patient.

Acute Disease↗

Swelling of Golgi vesicles in mammary secretory cells and its relation to the yield and quantitative composition of milk.

A quantitative description is given of some cellular secretory mechanisms in the mammary epithelium, that can be used in the interpretation of changes in milk yield and composition. The volume of the aqueous phase is considered to depend on a flux of vesicles derived from the Golgi apparatus and on the degree of vesicle swelling prior to exocytosis. Milk proteins secreted by the Golgi route are diluted during vesicle swelling and secreted fat globules are diluted to their final, milk, concentration in the alveolar lumen. Swelling of Golgi vesicles is considered to occur through an osmotic flow of water induced by the intravesicular synthesis of lactose and by the net transport of ions coupled to lactose synthesis. A hypothetical model is given of ion transport mechanisms across the Golgi vesicle membrane to illustrate how the coupling of lactose synthesis to salt transport might occur.

Animals↗

Structure of bovine milk calcium phosphate determined by X-ray absorption spectroscopy.

Calcium in cow's milk is mainly in the form of calcium phosphate-phosphoprotein complexes known as casein micelles. These micelles, in contrast to other phosphoprotein complexes in bone and other tissues, can be readily isolated and studied, but conventional techniques have given ambiguous and conflicting evidence on the structure of milk calcium phosphate. Extended X-ray absorption fine structure and near-edge structure measurements at the newly commissioned Synchrotron Radiation Source at Daresbury indicate that it closely resembles brushite, CaHPO4 X 2H2O. This result, and chemical analysis, requires that phosphate groups from the matrix phosphoproteins be incorporated in the brushite lattice, probably in the surface, suggesting that these organic phosphate groups act as heterogeneous nucleation sites for phase separation of the calcium phosphate from solution.

Animals↗

Sea urchin (lytechinus pictus) late-stage histone H3 and H4 genes: characterization and mapping of a clustered but nontandemly linked multigene family.

We have cloned and characterized members of a small multigene family that encodes late-stage histone H3 and H4 mRNAs from the sea urchin Lytechinus pictus. Unlike their highly repetitive histone gene counterparts, which are expressed at an earlier developmental stage, late H3 and H4 histone genes are not present in tandem repeats. In addition, the late stage H3 and H4 genes are not always tightly clustered together with the H1, H2A and H2B genes as they are in early histone genes. The spacer DNA that separates adjoining H3 and H4 coding regions is not conserved between nonallelic members of the late histone gene family. We have determined the nucleotide sequence of a continuous 2100 bp segment of DNA including both H3 and H4 coding sequences, the entire spacer DNA separating the genes and surrounding nonhistone DNA. The late histone H3 and H4 genes encode proteins identical to their early gene counterparts; however, the 5' leader sequence is shorter in late genes and the codon usage is different.

Animals↗

Inorganic constituents of milk. III. The colloidal calcium phosphate of cow's milk.

Experiments involving the depletion of milk calcium phosphate (MCP) with EDTA have shown that it has a Ca to phosphate ratio of 1.61 +/- 0.04, close to that of dental enamel. The calcium phosphate also contains small amounts of citrate (citrate/Pi = 0.097 +/- 0.011 and Mg (Mg/Pi = 0.044 +/- 0.011). These experiments and model calculations indicate that the Ca binding capacity of casein is not reduced by mineralization with calcium phosphate and hence that ion binding sites and nucleation sites are distinct, or nearly so. Calculations of the ionic equilibria in the aqueous phase of milk show that there is an invariant ion activity product for a molecular formula close to that of dicalcium phosphate. It is suggested that MCP is a mixture of salts, with dicalcium phosphate a precursor of more basic salts such as octacalcium phosphate and hydroxyapatite.

Animals↗

The inorganic constituents of milk. IV. Diffusible calcium and magnesium concentrations in goat's milk and the effect of starvation.

The concentrations of diffusible Ca and Mg in milk diffusates from 3 goats were determined before, during and after a 2-d period of starvation. Free Ca-concentrations were determined by a murexide method and compared with values calculated from a detailed model of the ion equilibria. It was shown that diffusible Ca increased as citrate increased during fasting and both decreased after refeeding, but there was a difference of about half a day in the response curves, with citrate following Ca. The difference was accounted for mainly by a change in free Ca2+ concentration which in turn was related mainly to changes in milk pH. Diffusible Mg underwent changes similar to those of diffusible Ca.

Animals↗

Building a ladder.

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Career Mobility↗

Cell movements in Xenopus eye development.

The vertebrate eye develops morphological markers, such as the ventral choroid fissure, which define its anatomical polarity in relation to the body. Also, retinal nerve fibres behave as though regionally differentiated by forming ordered, topographical maps of the visual field in the brain. It has long been held that these two features of eye polarity--its structure and the neural specificity of the ganglion cells--are labile in the early eye vesicle and become determined relative to body axes at a subsequent stage of development. Contrary to these earlier findings, recent experiments show that the structure and connectivity of the eye are already determined by the time it first appears as a distinct eye vesicle; surgical construction of eye pigmentation chimaeras suggested that normal tectal maps, previously reported after early eye rotations, may have arisen from neural retina cells recruited from the optic stalk after the operation. In agreement, using a radioactive tag which marks neural retina as well as pigment epithelium, I report here that during normal development in Xenopus laevis, cells in the ventral retina, where the choroid fissure forms, move into position from the optic stalk region during eye-cup formation. Depending on developmental stage, surgical eye rotations may intercept their movement and this provides a simple explanation of results previously taken to indicate a change from a labile to a determined state of eye polarity.

Animals↗

Post-secretory aggregation of caseins.

Particles as large as several micrometer diam. have been observed occasionally in normal milk and commonly in prepartum and postpartum colostrum. These particles can be dissociated by EDTA and their appearance closely resembles that of normal casein micelles. However, they are often too large to have been completely formed within the Golgi vesicles of mammary epithelium and hence some degree of post-secretory aggregation of caseins is thought to occur. Two possible mechanisms of post-secretory aggregation of caseins are: (1) a continuation of the normal processes of micelle assembly in the alveolus and (2) aggregation as a result of limited proteolysis of the caseins during the time the milk is in the mammary gland. Incubation of milk with fibrinolysin, however, failed to produce aggregation of normal micelles.

Animals↗

Inorganic constituents of milk: I. Correlation of soluble calcium with citrate in bovine milk.

A high correlation was found between soluble calcium and citrate concentrations during a study of seasonal changes in the composition of the commercial milk supply to South-west Scotland. A simple physicochemical model of the ion equilibria in the aqueous phase of milk suggests that the observed correlation is causal. This hypothesis was corroborated by an analysis of data on individual cow milks and by experiments involving the addition of citrate to milk at constant pH.

Animals↗

Measurement of particle sizes by elastic and quasi-elastic light scattering.

A method of measuring an average particle radius in a highly polydisperse dispersion using the wavelength dependence of turbidity is described. For particles which are no larger than 0.3 of the wavelength of light used, a polynomial representation of the scattering cross-section can be used. For larger particles, more extensive numerical calculations are required. The use of the method is illustrated by determining the average particle radius of casein micelles by both elastic and quasi-elastic light scattering techniques. A polydisperse homogeneous sphere model is found to be a reasonably accurate representation of casein micelles. Several modifications of the model which would improve the agreement between the two techniques are mentioned briefly.

Animals↗

Casein micelle size from elastic and quasi-elastic light scattering measurements.

The average molecular weight, particle radius and size distribution of particles in skim milk from eight cows in mid-lactation have been measured by means of elastic and quasi-elastic light scattering techniques. The properties of sub-micellar casein particles in the milk of each cow were also studied. Particular attention has been given to the effects of particle size heterogeneity in the interpretation of results. The weight average molecular weight of the particles from different cows varied from 2.6-10(8) to 15-10(8) and the corresponding average particle radius varied between 90 and 130 nm. An unusual feature of these particles is their high water content, which was found to vary from 2.4 to 6.4 ml/g with a positive correlation between average particle density and average particle mass. Variations in particle water content can be most readily understood in terms of a gel-like casein micelle.

Animals↗

The thermochemistry of reactions between alpha-s1-casein and calcium chloride.

The enthalpies of reactions between alpha-s1-casein and Ca2+ in solution were measured using a gradient layer calorimeter. The reactions are exothermic between 0 and 4.3 mM CaCl2. In the region of 4.3 mM CaCl2 there is a change to an endothermic reaction corresponding to micellisation. A calcium-binding curve has been obtained under the same conditions as the calorimetry experiments and this shows two sigmoidal binding phases. Turbidity measurements show that there is an association process corresponding to the second sigmoidal phase. A tentative interpretation of the heat curve in the region before micellisation is given in terms of the site binding of Ca2+, conformational changes in the protein and association. The main thermal processes are taken to be exothermic intramolecular hydrogen bonding induced by calcium binding and endothermic hydrophobic bonding.

Binding Sites↗